Experimental and clinical observations have supported the concept that the hypothalamus plays a key role in the regulation of adenohypophysial corticotropic cells secretory functions. Over 25 years ago, Guillemin, Rosenberg and Saffran and Schally independently demonstrated the presence of factors in hypothalamus which would increase the rate of ACTH secretion by the pituitary gland incubated in vitro or maintained in an organ culture. A physiologic corticotrop regulatory factor, CRF, was extracted from sheep hypothalamic fragments and characterized and synthesized by the Peptide Biology Laboratory at The Salk Institute, as described in Vale et al., Science 213:1394-1397, 1981.
Sauvagine is a 40-residue, amidated generally similar peptide, which was isolated from the skin of the South American frog Phyllomedusa sauvagei, characterized by Erspamer et al. and described in Regulatory Peptides, Vol. 2 (1981), pp. 1-13. Sauvagine has the formula: pGlu-Gly-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Ser-Leu-Glu-Leu-Leu-Arg-Lys-Met-Ile-G lu-Ile-Glu-Lys-Gln-Glu-Lys-Glu- Lys-Gln-Gln-Ala-Ala-Asn-Asn-Arg-Leu-Leu-Leu-Asp-Thr-Ile-NH.sub.2. Sauvagine has been reported to have biological activity in lowering blood pressure in mammals and in stimulating the secretion of ACTH and .beta.-endorphin.
UI has been isolated from urophyses of Catostomus commersoni (white sucker), purified and characterized as a polypeptide having the formula: H-Asn-Asp-Asp-Pro-Pro-Ile-Ser-Ile-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Asn-Met- Ile-Glu-Met-Ala-Arg-Ile-Glu-Asn-Glu- Arg-Glu-Gln-Ala-Gly-Leu-Asn-Arg-Lys-Tyr-Leu-Asp-Glu-Val-NH.sub.2, which is referred to as white sucker urotensin. The purification and characterization are described in an article by Lederis et al., Science Vol. 218, No. 4568, 162-164 (Oct. 8, 1982).